The most common manifestation of gastroesophageal reflux disease (GERD) is the symptom of heartburn, a substernal burning discomfort, often worse after meals and on reclining and temporarily relieved by antacids. Based on estimates that 20% of adults, ˜27 million people, have heartburn at least weekly, GERD is one of the most common conditions in Americans. It is also costly because of procedures used in diagnosis and in prescriptions for proton pump inhibitors (PPI) used in treatment, the latter now costing $13.9 billion dollars per year. Moreover, heartburn occurs at night as well as day (1), and so interferes with sleep and work, impairing both productivity and quality of life. Though rarely a cause of death, ⅓rd of GERD subjects have on esophagogastroduodenoscopy (EGD) erosive esophagitis, and this may progress to strictures or Barrett's esophagus, the latter a risk factor for esophageal adenocarcinoma. The remaining two-thirds with GERD have heartburn but a negative EGD and so are said to have nonerosive reflux disease (NERD) (2). For confirmation of NERD, many patients undergo 24 hour esophageal pH monitoring, a test performed using wire-based or wireless devices; however, both are time consuming, costly, oftentimes unpleasant and imperfect, with up to 50% of those with NERD having normal esophageal pH monitoring (3). This leaves approximately 9 million adults with a diagnosis of NERD based solely on history of heartburn or history of heartburn coupled with response to ‘empiric’ PPI therapy. Heartburn, however, is not specific for GERD, resulting in PPI therapy being over-prescribed and, because symptom response is often equivocal, continued for long periods even when ineffective. This situation could be avoided were there readily available biomarkers of GERD that enabled the clinician to diagnose GERD or more specifically NERD that is responsive to PPI therapy.
Accordingly, the present invention addresses the previous shortcomings of the art by providing methods for diagnosis of GERD through the detection of the biomarkers, E-cadherin N-terminal fragments and/or E-cadherin C-terminal fragments.